Sleep Outcomes and Multidimensional Assessment With Antiretroviral Therapy in People Living With HIV on Dolutegravir- vs Doravirine-Based Regimens (SOMNART)

Multidimensional Sleep Health in PLWH on DTG- vs DOR-Based ART: A Mixed-Methods Pilot Study

In South Africa, antiretroviral therapy (ART) has transformed HIV into a chronic, manageable condition, with high rates of viral suppression. As people living with HIV (PLWH) live longer, HIV care is increasingly focused on long-term health, quality of life, and prevention of non-communicable diseases such as obesity,cardiovascular disease, and metabolic disorders, which are increasingly common in this population. Sleep disturbance is highly prevalent among PLWH but is under-recognised in routine care. Poor sleep has been associated with adverse cardiometabolic, cognitive, and functional outcomes, yet is rarely systematically assessed in HIV programmes. Most existing evidence relies on subjective measures, with limited objective polysomnography data, particularly in African populations. In addition, the impact of different ART regimens on sleep health remains poorly understood. This study aims to evaluate and compare sleep health in virologically suppressed PLWH who switch from a dolutegravir-based regimen to a doravirine-based regimen versus thosewho remain on dolutegravir-based therapy. Sleep will be assessed using a multidimensional approach, incorporating polysomnography, actigraphy, and validated patient-reported outcome measures aligned with the RU-SATED framework. The study is particularly relevant in South Africa, where dolutegravir-based regimens are widely used and where obesity and metabolic disease are increasing. In a resource-limited setting where sleep disorders are often underdiagnosed, this study will generate locally relevant evidence on the relationship between ART and sleep health, with potential implications for more holistic HIV care.

Study Overview

• Status: Not yet recruiting
• Conditions: Sleep; HIV (Human Immunodeficiency Virus)
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate 300mg / Lamivudine 300mg / Dolutegravir 50mg; Drug: Tenofovir disoproxil fumarate 300mg / Lamivudine 300mg / Doravirine 100mg

Detailed Description

Background With the successful scale-up of antiretroviral therapy (ART), HIV infection has transitioned from a fatal disease to a chronic, manageable condition. This has led to substantial reductions in AIDS-related mortality globally and marked improvements in life expectancy among people living with HIV (PLWH), including in South Africa where ART coverage and viral suppression rates continue to rise. As a result, HIV care has increasingly shifted toward long-term health optimization, with growing attention to non-communicable diseases (NCDs) such as cardiovascular disease, obesity, and metabolic dysfunction.

Sleep disturbance is increasingly recognized as a potentially important but underappreciated contributor to morbidity in PLWH. Poor sleep is highly prevalent in this population and has been associated with adverse cardiometabolic, neurocognitive, and functional outcomes. Reported prevalence estimates of sleep disturbance in PLWH are as high as 50% or more, significantly exceeding that of the general population. However, most existing data rely on subjective questionnaires such as the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and screening tools for obstructive sleep apnoea (OSA). While these tools are useful for identifying symptoms, they are less sensitive to subtle or early physiological changes in sleep and may not adequately capture sleep as a multidimensional construct.

Contemporary sleep science conceptualises sleep health as a multidimensional construct encompassing satisfaction, alertness, timing, efficiency, duration, and regularity, rather than simply the absence of sleep disorders. Instruments such as RU-SATED have been developed to capture these domains; however, few studies have applied multidimensional sleep health frameworks in PLWH, and even fewer have evaluated how sleep health differs across antiretroviral regimens.

Objective sleep assessment using overnight polysomnography (PSG) provides a gold-standard method for characterising sleep architecture and physiology. PSG enables measurement of sleep stages (N1, N2, N3, and REM sleep), sleep continuity, respiratory events, oxygen desaturation, arousals, and other physiological parameters. Sleep architecture reflects the distribution of time spent across sleep stages, each of which plays distinct physiological roles. In healthy adults, sleep typically consists of approximately 50% N2, 20% N3 (slow-wave sleep), 25% REM sleep, and 5% N1 sleep, cycling throughout the night. N3 sleep is particularly important for physical restoration and metabolic regulation, while REM sleep is involved in emotional regulation and cognitive processing. Disruption of these stages, as well as sleep fragmentation and altered sleep continuity, has been associated with adverse health outcomes including cardiovascular disease, neurocognitive decline, and metabolic dysfunction.

Although PSG studies in PLWH are limited, existing evidence suggests consistent abnormalities in sleep architecture and continuity. Studies have reported reduced sleep efficiency, increased wake after sleep onset, altered distribution of sleep stages, reduced slow-wave sleep, and disrupted REM patterns in PLWH compared with HIV-negative controls. These abnormalities appear to persist even in virologically suppressed individuals on ART. Some evidence suggests that PLWH may exhibit increased vulnerability to sleep disruption in the presence of comorbid conditions such as obstructive sleep apnoea, with more pronounced effects on sleep architecture than in HIV-negative populations. Importantly, most PSG studies in PLWH have been conducted in predominantly male cohorts, limiting generalisability to women.

There is also significant interest in the potential role of antiretroviral agents in influencing sleep physiology. Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is well known to cause neuropsychiatric side effects, including insomnia and alterations in REM and slow-wave sleep. In contrast, dolutegravir (DTG), an integrase strand transfer inhibitor (INSTI), is widely used due to its efficacy and tolerability but has been associated with neuropsychiatric symptoms and weight gain in some studies. While weight gain associated with DTG is recognised, the potential role of sleep disturbance as a mechanistic pathway contributing to metabolic outcomes has not been well explored. Given the bidirectional relationship between sleep and weight regulation, it is plausible that changes in sleep architecture may contribute to or exacerbate metabolic risk in individuals receiving DTG-based regimens.

Doravirine (DOR), a newer NNRTI, appears to have a more favourable neuropsychiatric and metabolic profile compared with older agents. Clinical trials have reported lower rates of sleep-related adverse events in participants receiving DOR compared with EFV, and improvements in neuropsychiatric symptoms following switches to DOR-based regimens. However, no studies to date have directly assessed objective sleep architecture using polysomnography in individuals receiving DOR or compared its effects to DTG.

A critical gap therefore exists in understanding whether specific ART regimens differentially influence sleep health and sleep architecture over time, and whether these effects are clinically meaningful. In particular, it remains unclear whether sleep disturbance in PLWH is primarily driven by HIV infection itself, by antiretroviral agents, or by an interaction between the two.

Study Rationale This study is designed to address key gaps in understanding the relationship between ART, sleep health, and metabolic outcomes in PLWH. Specifically, it aims to determine whether DTG-based and DOR-based regimens differentially affect subjective sleep health and objective sleep architecture over time.

Given the increasing global burden of obesity and cardiometabolic disease in PLWH, understanding potential mechanistic links between ART, sleep, and metabolic outcomes is essential. Emerging evidence suggests that sleep quality, rather than sleep duration alone, may be more strongly associated with body mass index and long-term metabolic health. Therefore, identifying whether ART regimens differentially affect sleep quality may have important implications for long-term treatment selection and risk reduction.

Study Design This is a prospective, randomized, comparative study evaluating sleep outcomes in adults living with HIV initiating or switching to either a dolutegravir-based ART regimen or a doravirine-based ART regimen.

Participants will be assigned to one of two treatment groups:

DTG-based regimen (TDF/3TC/DTG; standard of care) DOR-based regimen (TDF/3TC/DOR)

The study will evaluate both subjective and objective sleep outcomes over time.

Significance This study addresses a major gap in HIV research by integrating multidimensional subjective sleep assessment with gold-standard objective sleep physiology measurements in a randomized comparative ART context in South Africa. It will provide novel evidence on whether DTG- and DOR-based regimens differentially affect sleep health, and whether these effects are clinically meaningful and associated with metabolic risk.

Findings will inform the design of a future fully powered clinical trial, including refinement of endpoints and sample size calculations, and may contribute to more individualized ART selection strategies that consider long-term sleep and metabolic health in PLWH.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bukani X Dyariwe; Phone Number: +27110844961; Email: bdyariwe@ezintsha.org
• Study Contact Backup: Name: Tarryn Collings, MBChB; Phone Number: +27110844982; Email: tcollings@ezintsha.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

-

Each participant must meet all the following criteria to be enrolled in this study:

1. Male or female aged 18-40 years
2. HIV-positive
3. Virologically suppressed, defined as HIV RNA <50 copies/mL
4. No known history of HIV treatment failure
5. On a stable first-line ART regimen for ≥ 12 months and TDF/3TC/DTG for ≥ 6 months prior to enrolment
6. BMI < 35 kg/m² and weight >35kg
7. Women of childbearing potential must have a negative pregnancy test at screening, must use acceptable contraception throughout the study, and must not be planning pregnancy during the study period
8. Willing and able to undergo overnight PSG as required by the protocol
9. Clinically stable with no uncontrolled comorbidities as assessed by the investigator
10. Able and willing to provide written informed consent

Exclusion Criteria:

-

Participants meeting any of the following criteria will be excluded from the study:

1. Planned or recent (30 days before enrolment) changes to chronic medication, or anticipated medication changes during the study period, if applicable
2. Known contraindication to Delstrigo (hepatic impairment, hypersensitivity, strong CYP450 inducers)
3. Previous NNRTI use or prior documented NNRTI mutations
4. Clinical suspicion of TB
5. Insufficient total sleep time on screening polysomnography to permit reliable interpretation of sleep parameters or to confirm or exclude a sleep disorder.

6. Evidence of a clinically significant sleep disorder at screening, based on history, the site-specific Sleep Disorders Screening Tool (SDST) and/or polysomnography, including but not limited to:

   1. Suspected or confirmed OSA
   2. Suspected or known insomnia
   3. Suspected restless legs syndrome (RLS), or periodic limb movements on PSG
   4. Narcolepsy

7. Use of medications known to significantly alter sleep, including (but not limited to):

   1. Benzodiazepines
   2. Non-benzodiazepine sedative-hypnotics
   3. Antipsychotics or mood stabilisers
   4. Antidepressants with significant sedating effects
   5. Isoniazid
   6. Anticonvulsants e.g. carbamazepine, phenytoin, phenobarbital
8. Current alcohol use disorder or substance use (including illicit substances) that may interfere with sleep or study assessments, as determined by the investigator.
9. Pregnant, breastfeeding, or planning to become pregnant during the study period, or currently nursing or caring for an infant younger than 6 months at home
10. Active psychiatric illness that might interfere with study procedures or overnight assessments, as assessed by the investigator
11. Regular shift work defined as working more than three nights or rotating shifts per month at baseline or during the study, or having transitioned from night-shift to day-shift duties within the past month
12. Known or suspected significant neurological conditions that may interfere with sleep (e.g., epilepsy, neurodegenerative disorders, or a history of moderate-to-severe traumatic brain injury).
13. Current participation in another clinical trial, observational or interventional

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TDF/3TC/DTG Arm; Tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg, and dolutegravir 50 mg (TDF/3TC/DTG; TLD) is the recommended first-line antiretroviral regimen for adults weighing ≥30 kg, according to the South African National ART Guidelines (2026). Participants randomised to continue TLD will serve as the control arm.	Drug: Tenofovir disoproxil fumarate 300mg / Lamivudine 300mg / Dolutegravir 50mg; Tenofovir disoproxil fumarate 300mg /lamivudine 300mg /dolutegravir 50mg (fixed dose combination tablet) one tab taken orally daily for the duration of the study.; Other Names: TLD
Experimental: TDF/3TC/DOR Arm; DELSTRIGO (TDF/3TC/DOR) is a three-drug combination of doravirine (a non-nucleoside reverse transcriptase inhibitor [NNRTI]), lamivudine, and tenofovir disoproxil fumarate (both nucleoside analogue reverse transcriptase inhibitors) and is indicated as a complete regimen for the treatment of HIV infection in adults and adolescent individuals weighing at least 35 kg. One tablet contains 100 mg of doravirine, 300 mg of lamivudine, and 300 mg of tenofovir disoproxil fumarate.	Drug: Tenofovir disoproxil fumarate 300mg / Lamivudine 300mg / Doravirine 100mg; DELSTRIGO is a three-drug combination of doravirine (a non-nucleoside reverse transcriptase inhibitor [NNRTI]), lamivudine, and tenofovir disoproxil fumarate (both nucleoside analogue reverse transcriptase inhibitors) and is indicated as a complete regimen for the treatment of HIV infection in adults and adolescent individuals weighing at least 35 kg. One tablet contains 100 mg of doravirine, 300 mg of lamivudine, and 300 mg of tenofovir disoproxil fumarate. Participants will be required to take one tablet PO daily for the duration of the study.; Other Names: Delstrigo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in RU-SATED total score from baseline to week 12	RU-SATED Questionnaire (Total Score: 0-24) Sleep health will be assessed using the RU-SATED sleep health questionnaire, a validated multidimensional measure comprising six domains of sleep health: Regularity, Satisfaction, Alertness, Timing, Efficiency, and Duration. Each domain is scored on a scale of 0-4, with higher scores indicating better sleep health. The total score ranges from 0 to 24, with higher scores reflecting overall better sleep health. The six items are as follows: Regularity: I go to sleep and wake up at about the same time every day. Duration: I sleep 7-9 hours per night. Timing: The midpoint of my sleep period is between 2:00 a.m. and 4:00 a.m. Efficiency: I am awake for less than 30 minutes between the time I go to bed and the time I get out of bed. Alertness: I stay awake all day without dozing. Satisfaction: I am satisfied with my sleep.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Between-Arm Difference in RU-SATED Total Sleep Health Score at Week 12	The RU-SATED questionnaire will be used to assess multidimensional sleep health across six domains: Regularity, Satisfaction, Alertness, Timing, Efficiency, and Duration. Each domain is scored from 0 to 4, with higher scores indicating better sleep health. The total RU-SATED score ranges from 0 to 24, with higher scores indicating better overall sleep health. Between-arm differences will compare mean RU-SATED total scores between participants switching from DTG-based ART to DOR-based ART and those continuing DTG-based ART at Week 12.	Week 12
Change from Baseline to Week 12 in Polysomnography-Derived Sleep Stage Distribution (N1, N2, N3, REM)	Sleep architecture will be assessed using overnight polysomnography (PSG). Sleep stage distribution (N1, N2, N3, and REM) will be expressed as percentage of total sleep time.	Baseline and Week 12
Change from Baseline to Week 12 in Polysomnography-Derived Sleep Latency	Sleep latency will be measured using overnight PSG and defined as the time from lights-off to sleep onset	Baseline and Week 12
Change from Baseline to Week 12 in Polysomnography-Derived REM Latency	REM latency will be measured using overnight PSG and defined as the time from sleep onset to the first epoch of REM sleep	Baseline and Week 12
Change from Baseline to Week 12 in Polysomnography-Derived Total Sleep Time	Total sleep time (TST) will be measured using PSG and defined as the total duration of sleep obtained during the recording period	Baseline and Week 12
Change from Baseline to Week 12 in Polysomnography-Derived Sleep Efficiency	Sleep efficiency will be measured using PSG and calculated as the percentage of time spent asleep while in bed	Baseline and Week 12
Change from Baseline to Week 12 in Polysomnography-Derived Wake After Sleep Onset	Wake after sleep onset (WASO) will be measured using PSG and defined as the total time spent awake after initial sleep onset	Baseline and Week 12
Change from Baseline to Week 12 in Polysomnography-Derived Apnea-Hypopnea Index	The apnea-hypopnea index (AHI) will be measured using PSG and defined as the number of apneas and hypopneas per hour of sleep	Baseline and Week 12
Change from Baseline to Week 12 in Polysomnography-Derived Oxygen Desaturation Events	Oxygen desaturation events will be measured using PSG and defined as episodes of reduced blood oxygen saturation during sleep below clinically defined thresholds	Baseline and Week 12
Change from Baseline to Week 12 in PROMIS Sleep Disturbance Short Form 8a T-score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) Short Form 8a and Sleep-Related Impairment (SRI) Short Form 8a will be used to assess subjective sleep health and daytime impairment. Each instrument produces a T-score with a mean of 50 and standard deviation of 10 in the general population, where higher scores indicate greater sleep disturbance or greater sleep-related impairment, respectively. The PROMIS SD SF 8a assesses perceptions of sleep quality, depth, and restfulness, while the PROMIS SRI SF 8a assesses perceived daytime functioning and alertness related to sleep.	Baseline and Week 12
Change from Baseline to Week 12 in PROMIS Sleep Related Impairment Short Form 8a T-score	The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) Short Form 8a and Sleep-Related Impairment (SRI) Short Form 8a will be used to assess subjective sleep health and daytime impairment. Each instrument produces a T-score with a mean of 50 and standard deviation of 10 in the general population, where higher scores indicate greater sleep disturbance or greater sleep-related impairment, respectively. The PROMIS SD SF 8a assesses perceptions of sleep quality, depth, and restfulness, while the PROMIS SRI SF 8a assesses perceived daytime functioning and alertness related to sleep.	Baseline and Week 12
Participant Recruitment Rate	Recruitment rate will be defined as the proportion of eligible participants who provide informed consent and are enrolled into the study out of all individuals screened for eligibility.	From initiation of recruitment until enrollment of the final participant, assessed over approximately 12 months
Participant Retention Rate Through Week 12	Retention rate will be defined as the proportion of enrolled participants who complete the study follow-up visit at Week 12.	Baseline and Week 12
Polysomnography Completion and Data Quality Success Rate	Polysomnography (PSG) success rate will be defined as the proportion of participants with technically adequate overnight PSG recordings that are suitable for analysis, including sufficient signal quality and complete sleep staging data.	Baseline and Week 12
Actigraphy Success Rate	Actigraphy success rate will be defined as the proportion of consenting participants with valid actigraphy recordings meeting predefined wear-time criteria (% complete ≥ 2 valid nights) sufficient for sleep parameter analysis.	Baseline and Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Internal consistency of the RU-SATED questionnaire measured by Cronbach's alpha	Preliminary psychometric evaluation of the RU-SATED questionnaire will be conducted, including internal consistency reliability (e.g., Cronbach's alpha).	Baseline and Week 12
Correlation between RU-SATED score and PROMIS Sleep Disturbance SF 8a	Convergent validity assessed via Spearman correlations between RU-SATED and PROMIS SD SF 8a	Baseline and Week 12
Sleep Duration Measured by Actigraphy at Baseline and Week 12	Actigraphy will be used to characterise habitual sleep patterns in the study cohort, including estimates of total sleep time.	Baseline and Week 12
Sleep Efficiency Measured by Actigraphy at Baseline and Week 12	Actigraphy will be used to characterise habitual sleep patterns in the study cohort, including sleep efficiency.	Baseline and Week 12
Number of Nocturnal Awakenings Measured by Actigraphy at Baseline and Week 12	Actigraphy will be used to characterise habitual sleep patterns in the study cohort, including the number of nocturnal awakenings.	Baseline and Week 12
Changes in Inflammatory Biomarkers from Baseline to Week 12	Changes in inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6), will be assessed from baseline to Week 12.	Baseline and Week 12
Sleep Quality Measured using a Numeric Rating Scale at Baseline and Week 12	A numeric rating scale for sleep quality will be evaluated for feasibility and differences between baseline and Week 12 will be assessed. Participants will be asked to rate their overall sleep quality in the past seven days using a 0-10 numeric rating scale.	Baseline and Week 12
Daytime Sleepiness Measured using the Pictorial Sleepiness Scale at Baseline and Week 12	A pictorial sleepiness scale will be evaluated for feasibility and values at baseline and Week 12 will be assessed. The pictorial sleepiness scale uses a series of cartoon faces to represent different levels of sleepiness and has been validated for use in South Africa	Baseline and Week 12
Change in Appetite Following Switch from Dolutegravir-Based to Doravirine-Based Antiretroviral Therapy	Changes in self-reported appetite will be assessed following the switch from dolutegravir-based antiretroviral therapy to doravirine-based antiretroviral therapy using a brief, site-derived questionnaire developed by the study team. The instrument consists of seven 7-day recall items designed to capture appetite and eating-related constructs relevant to a South African context, including food security (e.g., food availability and forced reduction of portion sizes), appetite intensity (unexpected hunger), eating control (ability to stop eating when full), and meal satisfaction. Each item is assessed using a 5-point Likert-type scale. Responses across the appetite and eating behaviour domains are summed to generate a total score out of 20, with higher scores indicating greater appetite and eating-related functioning. The two food security-related items will be analysed separately to reflect structural access to food rather than appetite behaviour.	Baseline and Week 12
Characterisation of Sleep Behaviours and Environmental Sleep Disruptors in a South African Context	Sleep behaviours, sleep patterns, and environmental sleep disruptors will be assessed using a General Sleep Questionnaire administered at screening. The questionnaire is designed to capture usual sleep habits and participant perceptions of sleep. This exploratory assessment represents an initial step toward characterising sleep in a South African population and informing the future development of contextually relevant sleep measurement tools for use in African settings.	Baseline

Collaborators and Investigators

• Sponsor: University of Witwatersrand, South Africa
• Investigators: Study Director: Francois WD Venter, PhD, Ezintsha, a division of Wits Health Consortium

Study record dates

Study Major Dates

• Study Start (Estimated): August 20, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: HIV; Antiretroviral Therapy; Sleep Health; Sleep Architecture; Delstrigo:
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Organophosphorus Compounds; Nucleosides; Deoxyribonucleosides; Organophosphonates; Adenine; Dideoxynucleosides; Zalcitabine; Tenofovir; Lamivudine; dolutegravir; doravirine
• Other Study ID Numbers: EZ-TC-041; 103974 (Other Grant/Funding Number: Merck Sharp & Dohme (MSD))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data that will be shared is all of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Immediately following publication
• IPD Sharing Access Criteria: Anyone who wishes to access the data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No